Cell type-specific changes in transcriptomic profiles of endothelial cells, iPSC-derived neurons and astrocytes cultured on microfluidic chips

Abstract

In vitro neuronal models are essential for studying neurological physiology, disease mechanisms and potential treatments. Most in vitro models lack controlled vasculature, despite its necessity in brain physiology and disease. Organ-on-chip models offer microfluidic culture systems with dedicated micro-compartments for neurons and vascular cells. Such multi-cell type organs-on-chips can emulate neurovascular unit (NVU) physiology, however there is a lack of systematic data on how individual cell types are affected by culturing on microfluidic systems versus conventional culture plates. This information can provide perspective on initial findings of studies using organs-on-chip models, and further optimizes these models in terms of cellular maturity and neurovascular physiology. Here, we analysed the transcriptomic profiles of co-cultures of human induced pluripotent stem cell (hiPSC)-derived neurons and rat astrocytes, as well as one-day monocultures of human endothelial cells, cultured on microfluidic chips. For each cell type, large gene expression changes were observed when cultured on microfluidic chips compared to conventional culture plates. Endothelial cells showed decreased cell division, neurons and astrocytes exhibited increased cell adhesion, and neurons showed increased maturity when cultured on a microfluidic chip. Our results demonstrate that culturing NVU cell types on microfluidic chips changes their gene expression profiles, presumably due to distinct surface-to-volume ratios and substrate materials. These findings inform further NVU organ-on-chip model optimization and support their future application in disease studies and drug testing.

Fluidic Circuit Board with Modular Sensor and Valves Enables Stand-Alone, Tubeless Microfluidic Flow Control in Organs-on-Chips

“…Devices were fabricated using an injection molding-like technique using a pair of negative replicate molds similar to a technique previously reported 26,27 . The HoC and the two respective negative molds were designed using SolidWorks (Dassault Systèmes, France).…”

Fluidic circuit board with modular sensor and valves enables stand-alone, tubeless microfluidic flow control in organs-on-chips

“…Devices were fabricated using an injection molding-like technique using a pair of negative replicate molds similar to a technique previously reported. 31,32 The HoC and the two respective negative molds were designed using SolidWorks (Dassault Systèmes, France). A CNC machine (Datron Neo, Datron AG) was used to micro mill the molds using 8 mm thick casted poly(methyl methacrylate) (PMMA) (Altuglass, France) as a stock material.…”

Induced pluripotent stem cell-based organ-on-a-chip as personalized drug screening tools: A focus on neurodegenerative disorders

“…Moreover, transcriptomic analysis showed enhanced maturity of iPSC-derived neurons and endothelial cells co-cultured with rat astrocytes in a microfluidic condition compared to standard cultures. 106 Therefore, OoC are a very interesting approach in the neuro-pharmaceutical field, and in combination with iPSC technology could lead to significant improvement in BBB-modeling.…”